Journal Article

Prospects of immune checkpoint modulators in the treatment of glioblastoma

Lim, Michael, Reardon, David A., Preusser, Matthias, Hafler, David A., Sampson, John H.

2015

Overview

Key Points The prognosis for glioblastoma patients is poor, with median overall survival of approximately 15–17 months Immunotherapy has clinical benefits in other advanced tumours, such as melanoma and lung cancer, for which conventional therapies have had limited success The blood–brain barrier prevents macromolecules from entering the CNS, but readily allows traffic of activated lymphocytes; thus, communication occurs between the CNS and the immune system The success of immunotherapy in other cancers, and the current understanding of the interaction between the brain and the immune system provide a rationale for exploration of immune checkpoint inhibitors in glioblastoma Tumour progression could involve multiple immunosuppressive mechanisms, making combination of immunotherapeutic agents that target different pathways a promising approach Clinical trials evaluating immune checkpoint inhibitors in glioblastoma patients are ongoing Glioblastoma is the most common primary brain tumour in adults, and has a notoriously poor prognosis. Recent successes of immunotherapy in other cancer types have made immunotherapy—particularly the use of immune checkpoint modulators—an appealing strategy against glioblastoma. Here, Matthias Preusser and colleagues summarize current knowledge on immune checkpoint modulators, and evaluate their potential role in glioblastoma treatment in light of preclinical studies and emerging clinical data. Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment—maximal safe resection and combination of radiotherapy with temozolomide chemotherapy—the median overall survival time is only approximately 15–17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/4028/67/1059/2325 / 692/699/375/1922 / Animals / Brain cancer / Brain Neoplasms - immunology / Brain Neoplasms - pathology / Brain Neoplasms - therapy / Brain research / Cancer therapies / Care and treatment / Clinical Trials as Topic / FDA approval / Glioblastoma - immunology / Glioblastoma - pathology / Glioblastoma - therapy / Glioblastoma multiforme / Humans / Immune system / Immunologic Factors - adverse effects / Immunologic Factors - therapeutic use / Immunotherapy / Immunotherapy - adverse effects / Immunotherapy - methods / Lung cancer / Medical prognosis / Medicine / Medicine & Public Health / Melanoma / Metastasis / Neurology / Patient outcomes / Pharmaceuticals / Prognosis / Radiation therapy / review-article / Tumors